225
Department of Pathophysiology and Therapy in Chronic Kidney Disease
Tatsuo Hosoya, Professor Iwao Ohno, Professor
Kimiyoshi Ichida, Professor Keitaro Yokoyama, Associate Professor
General Summary
Overview of education and research
This department aims to advance education and research to prevent the onset and devel- opment of chronic kidney disease (CKD) and to slow the increase in the number of patients with renal failure. The number of elderly patients undergoing hemodialysis (HD) for renal failure has increased markedly in Japan and has become a critical social and medical economic problem. One solution for this problem is to prevent the onset and progression of CKD and to reduce the number of patients requiring HD.
Another solution is to improve the quality of life for rehabilitation of patients who have already undergone HD and to promote home HD (HHD) and continuous ambulatory peri- toneal dialysis (CAPD) that can be performed at home. Both HHD and CAPD will greatly benefit patients undergoing HD, particularly patients who have difficulty visiting hospitals because of old age or disability. Furthermore, when the Great East Japan Earthquake occurred, it was shown that CAPD could be performed in disaster areas.
Research Activities
Prevention of CKD and its progression
Hyperuricemia has long be suggested to be a risk factor for the onset and progression of CKD, but definitive evidence was lacking, because an antihyperuricemic agent that could reduce uric acid levels effectively and safely in patients with renal dysfunction, such as CKD, was not available. Within the last 3 years, 2 novel antihyperuricemic agents that can be used effectively and safely in patients with renal dysfunction have been devel- oped. The efficacy and safety of one agent, febuxostat, were investigated in patients with CKD IIIb and IV and reported at academic meetings and in a paper. Furthermore, a double
-blind multicenter prospective clinical trial (FEATHER study: Febuxostat versus placebo randomized controlled trial regarding reduced renal function in patients with hyperuricemia complicated by chronic kidney disease stage 3) is in progress with more than 400 patients with CKD IIIab and hyperuricemia.
The utility and safety of topiroxostat, another novel antihyperuricemic agent, was investi- gated in patients with CKD III and hyperuricemia, and its effects on renal function, blood pressure, and albuminuria were examined. The result that albuminuria decreased signifi- cantly in patients receiving topiroxostat was reported in a paper. The underlying mecha- nism of reduced albuminuria is being investigated.
Research Activities 2013 The Jikei University School of Medicine
東京慈恵会 医科大学電子署名者 : 東京慈恵会医科大学 DN : cn=東京慈恵会医科大学, o, ou, [email protected], c=JP 日付 : 2015.03.16 10:54:20 +09'00'
226
Efforts to promote CAPD
To promote CAPD, a method of HHD, our department has employed peritoneal dialysis coordinators and had them visit the homes of patients undergoing CAPD to solve the problems presented by the patients and their families. The patients were then asked to answer a questionnaire survey about CAPD; the results were analyzed and presented at academic meetings. Because we believe that HHD by CAPD cannot be promoted with- out the cooperation of nursing care facilities and health and welfare facilities, CAPD study meetings have been held periodically with colleagues in such facilities near Kashiwa Hospital.
Combination therapy with HD once a week has been tried in patients undergoing CAPD with disturbed peritoneal function or insufficient water removal. A retrospective study and a prospective study (The study of evaluating adequateness replacement therapy:
EARTH Study) are ongoing as multicenter collaborative studies to elucidate effectiveness of the combination therapy.
Check
-up and evaluation
Research regarding the onset and development of hyperuricemia and CKD is ongo- ing. The analysis of the FEATHER study will be completed in 2 years, and a manuscript is being prepared. It is necessary to verify whether topiroxostat reduces albuminuria similarly in a variety of renal diseases and to elucidate the underlying mechanism in basic studies.
While CAPD has been promoted in patients with renal failure at the Department of Nephrology and Hypertension of our medical school, we hope other institutions will par- ticipate in this project and help establish the status of PD coordinators. To this end, we would like to make proposals for fulfillment of the systems for patients undergoing CAPD, such as medical insurance and nursing care insurance.
Publications
Kuriyama S, Sugano N, Takane K, Kobayashi A, Otsuka Y, Hosoya T. Intensive antihyperten- sive treatment with angiotensin receptor blocker combined with hydrocholorthiazide reduces urinary angiotensinogen in patients with type 2 diabetes mellitus. Open J Nephrol. 2013; 3: 89
-96.
Matsuo H
1, Ichida K
2, Takada T
3, Nakayama A
1, Nakashima H
1, Nakamura T
1, Kawamura Y
1, Takada Y
1, Yamamoto K
4, Inoue H
1, Oikawa Y
5, Naito M
6, Hishida A
6, Wakai K
6, Okada C
1, Shimizu S
1, Sakiyama M
1, Chiba T
1, Ogata H
1, Niwa K
5, Hosoyamada M
7, Mori A
8, Hamajima N
6, Suzuki H
3, Kanai Y
9, Sakurai Y
1, Hosoya T, Shimizu T
10, Shinomiya N
1(
1Nat Defense Med Coll,
2Tokyo Univ Pharm Life Sci,
3Univ Tokyo,
4
Kyushu Univ,
5Toho Univ,
6Nagoya Univ,
7Tei
kyo Univ,
8Seirei Prevent Health Care Ctr,
9
Osaka Univ,
10Midorigaoka Hosp). Common dysfunctional variants in ABCG 2 are a major cause of early
-onset gout. Sci Rep. 2013; 3: 2014.
Yokoyama K, Taniguchi M
1, Fukagawa M
2(
1Kyushu Univ,
2Tokai Univ). A Japanese approach for CKD
-MBD. Kidney Int Suppl (2011). 2013; 3: 451
-6.
Maruyama Y, Taniguchi M
1, Kazama JJ
1, Yokoyama K, Hosoya T, Yokoo T, Shigematsu T
2, Iseki K
1, Tsubakihara Y
1(
1Jpn Soc Dialysis Ther,
2Wakayama Med Univ). A higher serum alkaline phosphatase is associated with the inci- dence of hip fracture and mortality among patients receiving hemodialysis in Japan. Nephrol Dial Transplant. 2014; 29: 1532
-8. Epub 2014 Mar 18. Watanabe K, Yokoyama K, Yoshida H, Tanno Y, Ohkido I, Yokoo T. Chest X
-ray may serve as a screening examination for coronary artery cal- cification in dialysis patients. Kidney Int. 2014;
85: 710.
Sugano N, Yokoyama K, Kato N
1, Hara Y, Endo S, Mitome J, Kin T
2, Tokudome G
3, Kuri
yama S, Hosoya T, Yokoo T (
1Shinagawa Jin Clin,
2Kawagoe Ekimae Clin,
3Tokyu Hosp).
Research Activities 2013 The Jikei University School of Medicine
227
Monitoring of body water composition by the simultaneous use of bioelectrical impedance analy- sis and Crit
-LineR during hemodialysis. Clin Exp Nephrol. 2014 Feb 12. Epub ahead of print.
Kobayashi S, Ogura M, Hosoya T. Acute neu- tropenia associated with initiation of febuxostat therapy for hyperuricaemia in patients with chronic kidney disease. J Clin Pharm Ther. 2013; 38:
258
-61.
Tsuboi N, Utsunomiya Y, Hosoya T. Obesity
-related glomerulopathy and the nephron comple- ment. Nephrol Dial Transplant. 2013; 28 Suppl4:
iv108
-13.
Terawaki H
1, Yamagishi S
2, Funakoshi Y
3, Ma
tsuyama Y
4, Terada T
4, Nakayama K
5, Ogura M, Hosoya T, Ito S
5, Era S
4, Nakayama M
1(
1Fuku
shima Med Univ,
2Kurume Univ,
3Funakoshi Clin,
4Gifu Univ,
5Tohoku Univ). Pigment epi- thelium
-derived factor as a new predictor of mor- tality among chronic kidney disease patients treat- ed with hemodialysis. Ther Apher Dial. 2013; 17:
625
-30.
Miyazaki Y, Shimizu A, Ichikawa I
1, Hosoya T, Pastan I
2, Matsusaka T
1(
1Tokai Univ,
2Nat Cancer Inst). Mice are unable to endogenously regenerate podocytes during the repair of immu- notoxin
-induced glomerular injury. Nephrol Dial Transplant. 2014; 29: 1005
-12. Epub 2013 Dec 8. Stiburkova B
1, Sebesta I
1, Ichida K
2, Naka
mura M
2, Hulkova H
1, Krylov V
3, Kryspinova L, Jahnova H
1(
1Charles Univ,
2Tokyo Univ Pharm Life Sci,
3Univ Coll London). Novel allelic vari- ants and evidence for a prevalent mutation in URAT 1 causing renal hypouricemia: biochemical, genetics and functional analysis. Eur J Hum Genet. 2013; 21: 1067
-73.
Zeniya M, Nakano M, Saeki C, Yokoyama K, Ishikawa T
1, Takaguchi K
2, Takahashi H (
1Sai
seikai Niigata Daini Hosp,
2Kagawa Pref Cen
tral Hosp). Usefulness of combined application of double
-filtration plasmapheresis and twice
-daily injections of interferon
-β in hemodialysis patients with hepatitis C virus genotype 1b infection and a high viral load. Hepatol Res. 2014; 44: E 257
-60. Epub 2013 Sep 17.
Kuriyama S, Yokoyama K, Hara Y, Sugano N, Yokoo T, Hosoya T. Effect of aliskiren in chronic kidney disease patients with refractory hyperten- sion undergoing hemodialysis: a randomized con- trolled multicenter study. Clin Exp Nephrol. 2014;
18: 821
-30. Epub 2013 Nov 20.
Ito I
1, Waku T
2, Aoki M
1, Abe R
3, Nagai Y
3, Watanabe T
1, Nakajima Y
1, Ohkido I, Yoko
yama K, Miyachi H
4, Shimizu T
2, Murayama A
1, Kishimoto H
1, Nagasawa K
3, Yanagisawa J
1(
1Univ Tsukuba,
2Univ Tokyo,
3Tokyo Univ Agric Technol,
4Okayama Univ). A nonclassi- cal vitamin D receptor pathway suppresses renal fibrosis. J Clin Invest. 2013; 123: 4579
-94.
Matsuo H
1, Nakayama A
1, Sakiyama M
1, Chiba T
1, Shimizu S
1, Kawamura Y
1, Nakashima H
1, Nakamura T
1,2, Takada Y
1, Oikawa Y
3, Takada
T
4, Nakaoka H
5, Abe J
1, Inoue H
1, Wakai K
6, Kawai S
6, Guang Y
6,7, Nakagawa H
6, Ito T
1, Niwa K
3, Yamamoto K
8, Sakurai Y
1, Suzuki H
4, Hosoya T, Ichida K
9, Shimizu T
10, Shinomiya N
1(
1Nat Defense Med Coll,
2RIKEN,
3Toho Univ,
4
Univ Tokyo,
5Nat Inst Genet,
6Nagoya Univ,
7
Seinan Jogakuin Univ,
8Kyushu Univ,
9Tokyo Univ Pharma Life Sci,
10Midorigaoka Hosp).
ABCG 2 dysfunction causes hyperuricemia due to both renal urate underexcretion and renal urate overload. Sci Rep. 2014; 4: 3755.
Hosoya T, Ohno I, Nomura S
1, Hisatome I
2, Uchida S
3, Fujimori S
3, Yamamoto T
4, Hara S
5(
1Suzuka Kaisei Hosp,
2Tottori Univ,
3Teikyo Univ,
4Hyogo Coll Med,
5Toranomon Hosp).
Effects of topiroxostat on the serum urate levels and urinary albumin excretion in hyperuricemic stage 3 chronic kidney disease patients with or without gout. Clin Exp Nephrol. 2014 Jan 22. Epub ahead of print.
Nakao M, Yokoyama K, Yamamoto I, Matsuo N, Tanno Y, Ohkido I, Hayakawa H, Ikeda M, Yamamoto H, Hosoya T. Risk factors for encapsulating peritoneal sclerosis in long
-term peritoneal dialysis: a retrospective observational study. Ther Apher Dial. 2014; 18: 68
-73.
Hosoya T, Kimura K
1, Itoh S
2, Inaba M
3, Uchida S
4, Tomino Y
5, Makino H
6, Matsuo S
7, Yama
moto T
8, Ohno I, Shibagaki Y
1, Iimuro S
9, Imai N
1, Kuwabara M
10, Hayakawa H (
1St. Marianna Univ Sch Med,
2Tohoku Univ,
3Osaka City Univ,
4Teikyo Univ,
5Juntendo Univ,
6Okayama Univ,
7Nagoya Univ,
8Hyogo Coll Med,
9Univ Tokyo Hosp,
10Toranomon Hosp). The effect of febuxostat to prevent a further reduction in renal function of patients with hyperuricemia who have never had gout and are complicated by chronic kidney disease stage 3: study protocol for a multi- center randomized controlled study. Trials. 2014;
15: 26.
Miyazaki Y, Shimizu A
1, Pastan I
2, Taguchi K
3, Naganuma E
3, Suzuki T
3, Hosoya T, Yokoo T, Saito A
4, Miyata T
3, Yamamoto M
3, Matsusaka T
1(
1Tokai Univ,
2NIH,
3Tohoku Univ,
4Niigata Univ). Keap1 inhibition attenuates glomerulo- sclerosis. Nephrol Dial Transplant. 2014; 29:
783
-91. Epub 2014 Feb 11.
Kurashige M
1, Hanaoka K, Imamura M
1, Udagawa T, Kawaguchi Y
2, Hasegawa T
2, Hosoya T, Yokoo T, Maeda S
1(
1RIKEN,
2
Kanagawa Pref Shiomidai Hosp). A compre- hensive search for mutations in the PKD 1 and PKD 2 in Japanese subjects with autosomal domi- nant polycystic kidney disease. Clin Genet. 2014 Mar 10. Epub ahead of print.
Yokoyama K, Akiba T
1, Fukagawa M
2, Nakayama M
3, Sawada K
4, Kumagai Y
5, Cher
tow GM
6, Hirakata H
7(
1Tokyo Women’s Med Univ,
2Tokai Univ,
3Fukushima Med Univ,
4
Akita Univ,
5Kitasato Univ,
6Stanford Univ,
7
Jpn Red Cross Fukuoka Hosp). A random-
ized trial of JTT
-751 versus sevelamer hydrochlo-
ride in patients on hemodialysis. Nephrol Dial
Research Activities 2013 The Jikei University School of Medicine
228
Transplant. 2014; 29: 1053
-60. Epub 2013 Dec 26. Yokoyama K, Hirakata H
1, Akiba T
2, Fukagawa M
3, Nakayama M
4, Sawada K
5, Kumagai Y
6, Block GA
7(
1Jpn Red Cross Fukuoka Hosp,
2
Tokyo Women’s Med Univ,
3Tokai Univ,
4
Fukushima Med Univ,
5Akita Univ,
6Kitasato Univ,
7Denver Nephrologists). Ferric itrate hydrate for the treatment of hyperphosphatemia in nondialysis
-dependent CKD. Clin J Am Soc Nephrol. 2014; 9: 543
-52.
Iida R, Yokoyama K, Ohkido I, Tabei I, Takeyama H, Suzuki A
1, Shibasaki T
1, Matsu ba D, Suda N, Hosoya T (
1Keio Univ). Detection of dihydropyridine
-and voltage
-sensitive intracel- lular Ca
2+signals in normal human parathyroid cells. J Physiol Sci. 2013; 63: 235
-40.
Tomioka NH
1, Nakamura M
2, Doshi M
1, De guchi Y
1, Ichida K
2, Morisaki T
3, Hoso
yamada M
1(
1Teikyo Univ,
2Tokyo Univ Pharm Life Sci,
3Nat Cereb Cardiovasc Ctr Res Inst).
Ependymal cells of the mouse brain express urate transporter 1 (URAT 1). Fluids Barriers CNS.
2013; 10: 31.
Sakiyama M
1, Matsuo H
1, Shimizu S
1, Chiba T
1, Nakayama A
1, Takada Y
1, Nakamura T
1, Takada T
2, Morita E
3, Naito M
3, Wakai K
3, Inoue H
1, Tatsukawa S
1, Sato J
1, Shimono K
4, Makino T
5, Satoh J
1, Suzuki H
2, Kanai Y
6, Hamajima N
3, Sakurai Y
1, Ichida K
7, Shimizu T
8, Shinomiya N
1(
1Nat Defense Med Coll,
2
Univ Tokyo Hosp,
3Nagoya Univ,
4Toho Univ,
5
Nagoya City Univ,
6Osaka Univ,
7Tokyo Univ Pharmacy Life Sci,
8Midorigaoka Hosp).
Common variant of leucine
-rich repeat
-containing 16A (LRRC 16A) gene is associated with gout sus- ceptibility. Hum Cell. 2014; 27: 1
-4.
Nakayama A
1, Matsuo H
1, Shimizu T
2, Ogata H
1, Takada Y
1, Nakashima H
1, Nakamura T
1, Shimizu S
1, Chiba T
1, Sakiyama M
1, Ushiyama C
3, Takada T
4, Inoue K
5, Kawai S
6, Hishida A
6, Wakai K
6, Hamajima N
6, Ichida K
5, Sakurai Y
1, Kato Y
2, Shimizu T
7, Shinomiya N
1(
1Nat Defense Med Coll,
2Kanazawa Univ,
3Toho Univ,
4Univ Tokyo,
5Tokyo Univ Pharm Life Sci,
6
Nagoya Univ,
7Midorigaoka Hosp). Common missense variant of monocarboxylate transporter 9 (MCT 9/SLC 16A 9) gene is associated with renal overload gout, but not with all gout susceptibil- ity. Hum Cell. 2013; 26: 133
-6.
Ohno I, Hayashi H
1, Aonuma K
2, Horio M
3, Kashihara N
4, Okada H
5, Komatsu Y
6, Tamura S
7, Awai K
8, Yamashita Y
9, Kuwatsuru R
10, Hirayama A
11, Saito Y
12, Murohara T
13, Tamaki N
14, Sato A
2, Takayama T
11, Imai E
13, Yasuda Y
13, Koya D
15, Tsubakihara Y
3, Horie S
16, Korogi Y
17, Narumi Y
18, Hayakawa K
19, Daida H
10, Node K
20, Kubota I
21(
1Nippon Med Sch,
2Univ Tsukuba,
3Osaka Univ,
4Kawasaki Med Sch,
5
Saitama Med Univ,
6St. Luke’s Int Hosp,
7Univ Miyazaki,
8Hiroshima Univ,
9Kumamoto Univ,
10
Juntendo Univ,
11Nihon Univ,
12Nara Med Univ,
13Nagoya Univ,
14Hokkaido Univ,
15
Kanazawa Med Univ,
16Teikyo Univ,
17Univ Occup Environment Health,
18Osaka Med Coll,
19
